Machine intelligence decrypts ?-lapachone as an allosteric 5-lipoxygenase inhibitor.
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ABSTRACT:
SUBMITTER: Rodrigues T
PROVIDER: S-EPMC6138237 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor.
Rodrigues Tiago T Werner Markus M Roth Jakob J da Cruz Eduardo H G EHG Marques Marta C MC Akkapeddi Padma P Lobo Susana A SA Koeberle Andreas A Corzana Francisco F da Silva Júnior Eufrânio N EN Werz Oliver O Bernardes Gonçalo J L GJL
Chemical science 20180717 34
Using machine learning, targets were identified for β-lapachone. Resorting to biochemical assays, β-lapachone was validated as a potent, ligand efficient, allosteric and reversible modulator of 5-lipoxygenase (5-LO). Moreover, we provide a rationale for 5-LO modulation and show that inhibition of 5-LO is relevant for the anticancer activity of β-lapachone. This work demonstrates the power of machine intelligence to deconvolute complex phenotypes, as an alternative and/or complement to chemoprote ...[more]
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